RESUMEN
BACKGROUND: Difficult mask ventilation is common and is known to be associated with sleep-disordered breathing (SDB). It is our hypothesis that the incidence of expiratory retropalatal (RP) airway closure (primary outcome) during nasal positive pressure ventilation (PPV) is more frequent in patients with SDB (apnea hypopnea index ≥5 h-1) than non-SDB subjects. METHODS: The severity of SDB was assessed before surgery using a portable sleep monitor. In anaesthetized and paralysed patients with (n=11) and without SDB (n=9), we observed the behaviour of the RP airway endoscopically during nasal PPV with the mouth closed and determined the dynamic RP closing pressure, which was defined as the highest airway pressure above which the RP airway closure was reversed. The static RP closing pressure was obtained during cessation of mechanical ventilation in patients with dynamic RP closure during nasal PPV. RESULTS: The expiratory RP airway closure accompanied by expiratory flow limitation occurred more frequently in SDB patients (9/11, 82%) than in non-SDB subjects (2/9, 22%; exact logistic regression analysis: P=0.022, odds ratio 3.6, 95% confidence interval 1.1-15.4). Receiver operating characteristic curve analyses indicated AHI >10h-1 and presence of habitual snoring as clinically useful predictors for the occurrence of RP closure during PPV. Dynamic RP closing pressure was greater than the static RP closing pressure by approximately 4-5 cm H2O. CONCLUSIONS: Valve-like dynamic RP closure that limits expiratory flow during nasal PPV occurs more frequently in SDB patients.
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Anestesia General , Paladar Blando/fisiopatología , Respiración con Presión Positiva/métodos , Síndromes de la Apnea del Sueño/fisiopatología , Apnea Obstructiva del Sueño/fisiopatología , Administración Intranasal , Adulto , Anciano , Obstrucción de las Vías Aéreas/epidemiología , Obstrucción de las Vías Aéreas/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Parálisis/inducido químicamente , Polisomnografía , RonquidoRESUMEN
OBJECTIVE: To assess and risk-stratify the medium-term clinical outcomes after infrainguinal bypass grafting (IBG) to treat critical limb ischaemia (CLI) in patients with end-stage renal disease. METHODS: This was a retrospective single-centre study. Between April 2007 and March 2011, 112 limbs from 89 patients were studied. In particular, amputation-free survival (AFS), 30 day mortality, freedom from major adverse limb events (MALE), limb salvage, and overall survival were examined. The aim was to identify outcome predictors. RESULTS: Eight patients (9%) died within 30 days of IBG. The only positive predictor of 30-day mortality was an ejection fraction (EF) < 40% (hazard ratio [HR] 5.57, 95% confidence interval [CI] 1.16-26.83; p = .03). The mean follow-up duration was 14 months. The 1- and 2-year AFS rates were 64% and 43%, respectively, and the rates of freedom from MALE were 81% and 77%, respectively. In addition, the 1- and 2-year limb salvage rates were 89% and 85%, and the survival rates were 68% and 50%, respectively. Non-ambulatory status was negatively associated with AFS (HR 3.04, 95% CI 1.59-5.82; p < .01), freedom from MALE (HR 4.98, 95% CI 1.91-12.96; p < .01), and limb salvage (HR 5.18, 95% CI 1.47-18.30; p = .01). The other negative predictors of overall survival were a serum albumin level <3.0 g/dL (HR 2.26, 95% CI 1.12-4.58; p = .02) and an EF <40% (HR 2.24, 95% CI 1.05-4.79; p = .04). CONCLUSION: Patients with CLI on dialysis enjoyed satisfactory freedom from MALE and limb salvage, but survival and AFS were significantly less than reported for IBG in patients with CLI who did not receive dialysis. In addition, patients with an EF <40%, lower serum albumin (<3.0 g/dL), or non-ambulatory status experienced particularly poor clinical outcomes after IBG.
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Isquemia/cirugía , Fallo Renal Crónico/terapia , Diálisis Renal , Injerto Vascular , Anciano , Anciano de 80 o más Años , Amputación Quirúrgica , Biomarcadores/sangre , Enfermedad Crítica , Supervivencia sin Enfermedad , Femenino , Humanos , Isquemia/complicaciones , Isquemia/diagnóstico , Isquemia/mortalidad , Isquemia/fisiopatología , Japón , Estimación de Kaplan-Meier , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/mortalidad , Recuperación del Miembro , Masculino , Modelos de Riesgos Proporcionales , Diálisis Renal/efectos adversos , Diálisis Renal/mortalidad , Reoperación , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Albúmina Sérica/metabolismo , Albúmina Sérica Humana , Volumen Sistólico , Factores de Tiempo , Resultado del Tratamiento , Injerto Vascular/efectos adversos , Injerto Vascular/mortalidadRESUMEN
INTRODUCTION: Many reports show that denture adhesives improve the retention and stability of dentures. However, few randomized controlled trials have examined the effects of denture adhesives. OBJECTIVE: This 10-center randomized controlled trial with parallel groups involving 200 edentulous patients wearing complete dentures aimed to evaluate the effects of short-term use of cream and powder denture adhesives. METHODS: Patients were allocated into 2 cream- and powder-type adhesive groups and 1 control group. Intervention groups were treated with the 2 adhesives (1 each), and the control group received saline solution. Adhesive or control was applied to the denture-mucosal surface for 4 d, and data at baseline and after day 4 of intervention (i.e., 8 meals) were obtained. Patient satisfaction was evaluated with a 100-mm visual analog scale. Oral health-related quality of life was measured with the Japanese version of the Oral Health Impact Profile for Edentulous Patients. Perceived chewing ability was evaluated by a questionnaire regarding ease of chewing and swallowing food. Between-group comparisons were performed with Kruskal-Wallis tests with the Mann-Whitney U test adjusted by Bonferroni correction. Within-group comparisons of pre- and postintervention measurements were performed with the Wilcoxon signed-rank test. Intention-to-treat analysis was also performed. RESULTS: Between-group comparisons showed no significant differences for general satisfaction or Oral Health Impact Profile for Edentulous Patients. However, significant differences in satisfaction with various denture functions with cream- and powder-type adhesives were seen in pre- and postintervention comparisons (P < 0.05). Significant differences were also observed for perceived chewing ability of hard foods (P < 0.05). CONCLUSION: These results suggest that although denture adhesives do not invariably improve denture function, they do affect subjective evaluations and possibly chewing of hard foods. Therefore, the effects of denture adhesive use are insufficient to resolve any fundamental dissatisfaction with dentures ( ClinicalTrials.gov NCT01712802 ). KNOWLEDGE TRANSFER STATEMENT: The results of this study suggest that denture adhesives should be applied under certain conditions; however, an appropriate diagnosis is important before application. These practice-based data provide information to establish evidence-based guidelines for applying denture adhesives.
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Retención de Dentadura , Boca Edéntula , Cementos Dentales , Dentadura Completa , Humanos , Calidad de VidaRESUMEN
The aim of this study was to biomechanically evaluate the primary stability of pure titanium orthodontic mini-implants, inserted into pre-drilled cavities of differing diameters. Mini-implants (1.2 mm diameter) were placed into 1.0 mm and 1.2 mm diameter cavities prepared in the mid-region of the bilateral hind leg femurs of anesthetized beagles. Removal torque strengths were measured immediately, 1, 3, 6, 9 and 12 weeks post-insertion of the implant. For mini-implants placed into 1-mm cavities, removal torque values decrease over the first 6 weeks (p<0.01), after which values remained static. Average values obtained immediately, 1, 3 and 6 weeks post-insertion were 10.98, 8.83, 7.20 and 5.12 Ncm, respectively . Immediately post-insertion, removal torque values of mini-implants placed in a 1.2-mm cavity, were 11-fold lower than those placed in 1.0-mm cavities, which then demonstrated a significant increase in strength from 3 weeks (1.35 Ncm) to 6 weeks (5.17 Ncm) post-insertion (p<0.01). Measurements 6, 9 and 12 weeks post-insertion were similar to those in the 1.0-mm cavity. Initial stability of titanium mini-implants is considered necessary for immediate and early use in orthodontics, and an implant without this initial stability should be replaced or isolated until it develops the appropriate stability supported by osseointegration.
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Implantes Dentales , Materiales Dentales , Fémur/cirugía , Métodos de Anclaje en Ortodoncia/instrumentación , Titanio , Animales , Fenómenos Biomecánicos , Tornillos Óseos , Perros , Ensayo de Materiales , Diseño de Aparato Ortodóncico , Osteotomía , Factores de Tiempo , TorqueRESUMEN
OBJECTIVE: The effect of the chronic administration of L-arginine on intimal thickness and the kinetics of smooth muscle cell proliferation in autovein grafts in hypercholesterolemic rabbits were examined. METHODS: Male rabbits were fed a 1% cholesterol diet (control group) and a 1% cholesterol diet supplemented by 2.25% L-arginine HCl in drinking water (arginine group). Each group underwent reversed autologous vein bypass grafting of the left common carotid artery using the left external jugular vein. At 2 or 4 weeks after operation, intimal cell proliferation was determined by 5-bromo-2'-deoxyuridine (BrdU) incorporation and intimal thickness of the graft was measured with an ocular cytometer. At 4 weeks after operation, endothelium-dependent responses were examined by isometric tension recording. RESULTS: At 4 weeks after operation, the level of plasma arginine and citrulline are significantly higher in the arginine group (n = 7), compared with the control (n = 7). Intimal thickness in the arginine group (n = 7) was significantly reduced, compared with that of the control (n = 7). At 2 weeks after operation, the BrdU labeling index of the control (n = 5) was significantly higher than that of the arginine group (n = 5). At 4 weeks after operation, ACh caused endothelium-dependent relaxation in the arginine group (n = 4), while in the control (n = 4), ACh did not relax. CONCLUSIONS: These results suggest that smooth muscle cell proliferation of the rabbit jugular vein grafts during hypercholesterolemia occurs at an early stage after graft implantation, prior to the development of intimal thickness. Intimal thickness of vein graft during hypercholesterolemia was reduced by chronic administration of dietary L-arginine, by inhibiting smooth muscle cell proliferation. The enhancement of NO production in the blood vessel wall may therefore be useful for preventing late graft failure.
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Arginina/administración & dosificación , Hipercolesterolemia/patología , Venas Yugulares/trasplante , Músculo Liso Vascular/patología , Acetilcolina/farmacología , Análisis de Varianza , Animales , Arginina/metabolismo , Bromodesoxiuridina/metabolismo , División Celular , Citrulina/sangre , Rechazo de Injerto/prevención & control , Hipercolesterolemia/metabolismo , Técnicas In Vitro , Venas Yugulares/efectos de los fármacos , Venas Yugulares/patología , Masculino , Músculo Liso Vascular/efectos de los fármacos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Norepinefrina/farmacología , Conejos , Túnica Íntima/efectos de los fármacos , Túnica Íntima/metabolismo , Túnica Íntima/patología , omega-N-Metilarginina/farmacologíaRESUMEN
Proteoglycans are known to play an important role in the mineralization process, acting either as promoters or inhibitors. In this study the binding affinity of a variety of constituent glycosaminoglycan to hydroxyapatite was studied. Glycosaminoglycans (10-1000 microg ml(-1) in 0.02 M sodium acetate (pH 6.8) were constantly circulated through a hydroxyapatite column for 1 h. The total amount of glycosaminoglycan bound was determined by dimethylmethylene blue assay. The relative affinities of the different glycosaminoglycans remaining bound to hydroxyapatite was investigated by examining their release in a 0-1 M sodium phosphate gradient. Differences were noted between the desorption profiles of dermatan sulfate with two elution peaks and chondroitin 4-sulfate and chondroitin 6-sulfate each with a single peak. Dermatan sulfate and chondroitin 6-sulfate had a higher affinity for hydroxyapatite than chondroitin 4-sulfate possibly due to the presence of differing di-sulfated disaccharide ratios in the glycosaminoglycan chains. These findings suggest the presence of a variety of binding forms of each glycosaminoglycan or the differing orientation of these forms to yield different complexes with hydroxyapatite. The Ca2+ co-ordinates of the glycosaminoglycans are known to vary and may in part explain these findings.
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Materiales Biocompatibles/química , Durapatita/química , Glicosaminoglicanos/química , Adsorción , Sitios de Unión , Cromatografía Liquida/métodos , Concentración de Iones de Hidrógeno , Cinética , Azul de Metileno/análogos & derivados , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Vascular smooth muscle cell (SMC) migration, proliferation and extracellular matrix protein production are key steps in the formation of intimal hyperplasia, a process that leads to failure of vascular reconstructions. Protein kinase C (PKC) may be involved in all 3 cellular events. PKC consists of a family of 11 isotypes, 8 of which we have identified in human vascular SMCs. In this study we evaluate the role of PKCalpha as a second messenger for proliferation, migration and fibronectin production induced by human saphenous vein SMCs. METHODS: DNA synthesis was evaluated by using (3)H-thymidine incorporation. Mitogen-activated protein kinase (MAP-K) activation was quantified by Western blotting with an antibody to its phosphorylated substrate, Elk-1. Chemotaxis was evaluated by using a microchemotaxis chamber. SMC fibronectin was measured by Western blotting. For all experiments, PKCalpha was blocked with a selective inhibitor, Gö6976. RESULTS: Gö6976, at concentrations that allow selective inhibition of PKCalpha, inhibited platelet-derived growth factor-stimulated SMC proliferation and MAP-K activation by 30% to 40% and 30% to 60%, respectively. SMC chemotaxis was stimulated approximately 2-fold by the PKCalpha inhibitor. Neither basal nor transforming growth factor-betaI induced fibronectin production was affected by Gö6976. CONCLUSIONS: Our data suggest that PKCalpha is a positive mediator of SMC proliferation and MAP-K activity, a negative regulator of migration and has no effect on SMC fibronectin production. These data suggest that modulating activities of specific PKC isotypes might be useful in both the study and control of intimal hyperplasia.
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Quimiotaxis/fisiología , Proteínas de Unión al ADN , Fibronectinas/biosíntesis , Isoenzimas/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Músculo Liso Vascular/citología , Músculo Liso Vascular/fisiología , Proteína Quinasa C/metabolismo , Vena Safena/citología , Vena Safena/fisiología , Factores de Transcripción , Carbazoles/farmacología , División Celular/efectos de los fármacos , División Celular/fisiología , Células Cultivadas , Quimiotaxis/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Humanos , Indoles/farmacología , Músculo Liso Vascular/efectos de los fármacos , Fosforilación , Proteína Quinasa C-alfa , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Vena Safena/efectos de los fármacos , Sistemas de Mensajero Secundario , Factor de Crecimiento Transformador beta/farmacología , Proteína Elk-1 con Dominio etsRESUMEN
We investigated the penetration of cisplatin into the mouse cerebral cortex-rich region (CCR) induced by lipopolysaccharide (LPS). With the injection of cisplatin into mice 3 h after the LPS treatment, platinum was detected in the CCR during the 7 days after the injection, while platinum was not detected in the CCR of cisplatin-injected mice without LPS pretreatment and of mice simultaneous treated with cisplatin and LPS. The N(G)-nitro-L-arginine methyl ester dose-dependently lowered the platinum level. A dose of 5 mg/kg of aminoguanidine reduced the increase in the platinum level of the LPS-treated mouse, and platinum was no longer detected at doses of 20 mg/kg in the aminoguanidine-injected group. At doses of 500 mg/kg aminoguanidine, however, no effect was seen on the platinum level of the CCR induced by LPS. Regarding indomethacin, the injection of 5 mg/kg resulted in a decrease in the platinum content of the CCR, but not undetectable level. These results suggest that LPS increases the penetration of cisplatin into the mouse brain, and platinum may be accumulated in the CCR. Nitric oxide and prostaglandins contribute to the penetration of platinum into the cerebral cortex.
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Antineoplásicos/farmacocinética , Barrera Hematoencefálica/efectos de los fármacos , Corteza Cerebral/metabolismo , Cisplatino/farmacocinética , Escherichia coli , Lipopolisacáridos/farmacología , Animales , Corteza Cerebral/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Electroforesis en Gel de Agar , Inhibidores Enzimáticos/farmacología , Guanidinas/farmacología , Indometacina/farmacología , Masculino , Ratones , NG-Nitroarginina Metil Éster/farmacología , Platino (Metal)/metabolismoRESUMEN
Glycosaminoglycans (GAG) were extracted from the connective tissue of the palatal rugae, separated by electrophoresis and compared with the results obtained for the remaining palatal mucosal and gingival connective tissues. The GAG content of the rugae (3.01 mg/g defatted dry weight) was higher than in the remaining palatal mucosa (2.33 mg/g defatted dry weight) or gingiva (1.68 mg/g defatted dry weight). Dermatan sulphate was the predominant GAG in both the palatal rugae (48% of total GAG) and the remaining palatal mucosa (50%) followed by hyaluronic acid (33 and 31% respectively). The results do not support previous histochemical observations in which the rugae appeared to be rich in hyaluronic acid.
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Glicosaminoglicanos/análisis , Mucosa Bucal/análisis , Hueso Paladar/análisis , Animales , Tejido Conectivo/análisis , Femenino , Encía/análisis , Macaca fascicularisRESUMEN
The submandibular gland proteoglycans were investigated biochemically and immunohistochemically in male Sprague-Dawley rats. Proteoglycans were extracted with 4 M guanidine-HCl, followed by ultracentrifugation in a CsCl density gradient, and fractionated by ion-exchange chromatography and gel filtration. The molecular weight of PGs was estimated by SDS-PAGE and immunoblot analysis with monoclonal antibodies (HepSS-1 or 6-B-6). The glycosaminoglycan side-chains in the proteoglycan fractions were identified by electrophoresis on cellulose acetate membrane. Three proteoglycan fractions were obtained. One was a heparan sulphate proteoglycan that migrated as a diffuse band of about 210 kDa. The other two fractions contained at least two dermatan sulphate proteoglycans of 70-85 kDa and 40-50 kDa. Digestion of these two proteoglycans with chondroitinase ABC, but not heparitinase, produced two bands of 50 and 21 kDa, which were core proteins. The smaller dermatan sulphate proteoglycan may be a portion of the other, as the core protein of both bound to 6-B-6 antibody, and sugar chains of both were the same (20-30 kDa). Heparan sulphates recognized by antibody HepSS-1 were observed widely in the basement membrane, fibrous connective tissue, and striated and excretory ductal cells, while dermatan sulphate proteoglycans recognized by antibody 6-B-6 were located in the connective tissue surrounding striated and excretory ducts.
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Proteoglicanos/química , Proteínas y Péptidos Salivales/química , Glándula Submandibular/química , Animales , Anticuerpos Monoclonales , Membrana Basal/química , Cromatografía en Gel , Cromatografía por Intercambio Iónico , Tejido Conectivo/química , Dermatán Sulfato/análisis , Electroforesis en Acetato de Celulosa , Electroforesis en Gel de Poliacrilamida , Heparitina Sulfato/análisis , Immunoblotting , Inmunohistoquímica , Masculino , Peso Molecular , Proteoglicanos/análisis , Ratas , Ratas Sprague-Dawley , Conductos Salivales/química , Proteínas y Péptidos Salivales/análisisRESUMEN
Gingival crevicular fluid (GCF) was collected into capillary tubes from healthy gingiva and sites of advanced periodontitis. Following digestion with Pronase E, the glycosaminoglycans were isolated by successive precipitation into 5% cetylpyridinium chloride and 95% ethanol. Unsaturated disaccharide isomers of chondroitin sulphate, obtained following chondroitinase ACII digestion, were analysed by high-performance liquid chromatography. Chondroitin sulphate was found in all GCF samples, with greater amounts in patients with periodontal disease than at control sites with a relatively healthy periodontium. The predominant isomer in the periodontal diseased group was delta Di-4S, while that in the control group and serum samples was delta Di-0S. Comparison of the relative proportions of the unsaturated disaccharides in GCF with previously reported values for alveolar bone, cementum, gingiva and periodontal ligament, as well as for serum, indicates that the chondroitin sulphate present in GCF of patients with periodontal disease originated from the mineralized connective tissues of the periodontium, notably alveolar bone, possibly with some contributions from soft connective tissues of gingiva and periodontal ligament and from serum.
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Sulfatos de Condroitina/química , Líquido del Surco Gingival/química , Adulto , Cromatografía Líquida de Alta Presión , Disacáridos/análisis , Humanos , Persona de Mediana Edad , Periodontitis/metabolismoRESUMEN
OBJECTIVE: The purpose of this study was to evaluate the efficacy of a newly developed antiplatelet agent, 4-cyano-5, 5-bis[methoxyphenyl]-4-pentenoic acid (E5510) on intimal hyperplasia of experimental autologous vein grafts in a distal poor runoff canine model. METHOD: The femoral vein was implanted into the femoral artery preparing a distal poor runoff model. These animals were divided into three groups consisting of the E5510 group, the Aspirin group, and the Control group. The vein grafts were harvested at either 1 or 4 weeks after implantation. RESULTS: At 4 weeks, the degree of intimal hyperplasia of the graft of E5510 group was significantly less than that of the Aspirin group and the Control group (p < 0.05). No significant difference was observed between the Aspirin group and the Control group. At 1 week, the degree of intimal cell proliferation was determined by bromodeoxyuridine (BrdU) incorporation and was expressed as the BrdU labeling index. The BrdU labeling index of the E5510 group was also significantly lower than that of the Control group (p < 0.05). CONCLUSIONS: These data demonstrate the efficacy of E5510 in reducing intimal hyperplasia of vein grafts under distal poor runoff conditions by reducing the degree of smooth muscle cell proliferation.
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Ácidos Grasos Monoinsaturados/farmacología , Vena Femoral/trasplante , Inhibidores de Agregación Plaquetaria/farmacología , Túnica Íntima/patología , Animales , Aspirina/farmacología , Velocidad del Flujo Sanguíneo , Bromodesoxiuridina/farmacología , División Celular/efectos de los fármacos , Perros , Arteria Femoral/cirugía , Vena Femoral/patología , Hiperplasia , Masculino , Agregación Plaquetaria/efectos de los fármacos , Túnica Íntima/efectos de los fármacosRESUMEN
BACKGROUND: It remains difficult for surgeons to choose between an in-flow and sequential arterial reconstruction in patients with multisegment arterial occlusive disease. In addition, the exact criterion for the proper revascularization procedures of these patients also remains obscure. METHODS: The profundapopliteal collateral index (PPCI) was determined in all patients with occlusions of both the aortoiliac and superficial femoral arteries prior to undergoing an arterial bypass. The PPCI in the inflow bypass (IB) was also compared with the sequential bypass (SB). RESULTS: The symptoms of all patients undergoing either IB or SB improved. Preoperatively, the average PPCI in IB patients was significantly lower than that in SB patients. In addition, no significant difference was observed in the increased average rate of the ankle brachial index (ABI) between IB and SB. CONCLUSIONS: The PPCI is an accurate predictor of the hemodynamic potential of the geniculate collaterals. In cases with a low PPCI, especially in patients with multisegment arterial occlusive disease, in-flow procedures alone may often be sufficient for the successful treatment of such patients. The PPCI is thus considered to be useful for selecting the optimal revascularization procedures.
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Angiografía , Arteriopatías Oclusivas/cirugía , Isquemia/cirugía , Pierna/irrigación sanguínea , Anciano , Arteriopatías Oclusivas/diagnóstico por imagen , Circulación Colateral/fisiología , Femenino , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/cirugía , Humanos , Isquemia/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Arteria Poplítea/diagnóstico por imagen , Arteria Poplítea/cirugía , Complicaciones Posoperatorias/diagnóstico por imagen , PronósticoRESUMEN
We investigated whether free radical scavengers and antioxidants inhibit the accumulation of platinum (Pt) in the cerebral cortex. Pt was detected in the cerebral cortex of mice after administration of cisplatin and exposure to short-term hypoxia. When mice were treated with either allopurinol (20 mg/kg) or catalase (100 mg/kg) before cisplatin administration and low oxygen exposure, Pt was not detected in the cerebral cortex. However, Pt was detected in the cerebral cortex of mice pretreated with either a low dosage of allopurinol or heat-denatured catalase. Furthermore, Pt was detected in the cerebral cortex of mice preadministered vitamin C, vitamin E, or deferoxamine. Lipid peroxide levels in the cerebral cortex increased 10 min after the treatment of hypoxia, and peaked 30 min after the treatment. These results suggested that short-term hypoxia produces free radicals, which allows Pt to pass through the blood-brain barrier and accumulate in the cerebral cortex, and that the production of free radicals is reduced by the administration of either allopurinol or catalase, which prevents Pt from passing through the barrier.
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Alopurinol/farmacología , Antioxidantes/farmacología , Catalasa/farmacología , Corteza Cerebral/metabolismo , Cisplatino/farmacocinética , Depuradores de Radicales Libres/farmacología , Peroxidación de Lípido/efectos de los fármacos , Platino (Metal)/farmacocinética , Animales , Ácido Ascórbico/farmacología , Corteza Cerebral/efectos de los fármacos , Hipoxia , Cinética , Masculino , Ratones , Ratones Endogámicos , Niacina/farmacología , Vitamina E/farmacologíaRESUMEN
The relationship between the accumulation of platinum in the cerebral cortex following cisplatin administration and injury to the blood-brain barrier after lipopolysaccharide (LPS) treatment was investigated. The appearance of intravenously injected fluorescein in the brain was significantly increased 10-24 h after LPS treatment, the effect being dose-dependent. Platinum was detectable in the cerebral cortex of cisplatin-treated mice 24 h after LPS treatment, but not without LPS treatment. In mice pretreated with α-tocopherol, LPS administration did not significantly augment fluorescein penetration into the brain, whereas pretreatment with either allopurinol or ascorbic acid did not modify the LPS-induced increase in fluorescein penetration. In contrast, platinum in the cerebral cortex after cisplatin administration was still detectable in the allopurinol-, ascorbic acid-, and α-tocopherol-pretreated groups, and the levels of platinum in these groups were not significantly different from those in the group treated with LPS only. Administration of superoxide dismutase (SOD), but not of catalase, tended to inhibit the penetration of fluorescein. Both SOD and catalase significantly lowered platinum content in the cerebral cortex following cisplatin administration in mice treated with LPS. Thus, free radicals may injure the blood-brain barrier in mice challenged with LPS, and allow cisplatin to penetrate into the cerebral cortex, resulting in platinum accumulation.
RESUMEN
We investigated the involvement of nitric oxide (NO) and prostaglandins (PGs) in the damage to the blood-brain barrier (BBB) induced by lipopolysaccharide (LPS), using fluorescein as a tracer in mice. Aminoguanidine, a competitive inhibitor of inducible NO synthase (iNOS), when administered s.c. at 5 mg/kg, but not 500 mg/kg, reduced significantly the increase in brain fluorescein level after its i.v. injection in LPS-treated mice. When 1000 mg/kg of l-arginine, a substrate of NOS, were co-administered with 5 mg/kg of aminoguanidine to LPS-treated mice, the inhibitory effect of aminoguanidine on the increased fluorescein level disappeared. N(G)-Nitro-l-arginine methyl ester (l-NAME), a non-isoenzyme-selective NOS inhibitor, when administered s.c. at 5 mg/kg, only slightly reduced the LPS-induced increase in the brain fluorescein level. A pretreatment with dexamethasone, which suppressed the induction of both iNOS and cyclooxygenase 2 (COX-2), tended to decrease the brain fluorescein level in LPS-treated mice. Indomethacin, a COX inhibitor, at 5 mg/kg, but not 10 mg/kg, suppressed significantly the LPS-induced increase in the brain fluorescein level. These results involve that both the NO produced by iNOS and the PGs produced by COX contribute to enhance BBB permeability in LPS-administered mice.
RESUMEN
Glycosaminoglycans (GAGs) in monkey palatal lamina propria plus both fatty and glandular zones of palatal submucosa were compared. Chemical analysis revealed that GAG contents of the lamina propria and glandular zone were higher than that of the fatty zone. The four GAGs identified by electrophoretic analysis were hyaluronic acid, dermatan sulfate, chondroitin sulfate and heparan sulfate. Each mucosal layer contained all four GAG components. The predominant GAG in both the lamina propria and glandular zone was dermatan sulfate followed by hyaluronic acid. The reverse situation (predominant hyaluronic acid, less prominent dermatan sulfate) was noted in the fatty zone of the submucosa. The three tissue regions showed different molar ratios of unsaturated chondroitin sulfate disaccharides. The ratio of delta Di-4S to delta Di-6S was lower in the lamina propria than in either the fatty or glandular submucosal zones.
Asunto(s)
Glicosaminoglicanos/análisis , Mucosa Bucal/química , Hueso Paladar/química , Animales , Sulfatos de Condroitina/análisis , Dermatán Sulfato/análisis , Electroforesis en Acetato de Celulosa , Femenino , Encía/química , Heparitina Sulfato/análisis , Histocitoquímica , Ácido Hialurónico/análisis , Macaca fascicularisRESUMEN
We determined the hyaluronic acid disaccharides, delta Di-HA, in the gingival crevicular fluid (GCF) and whole saliva of patients with periodontal disease, and in the peri-implant sulcus fluid (PISF) from sites around titanium osseointegrated implants, and compared these values with those in the GCF and whole saliva of controls. We also determined values for chondroitin sulfate disaccharide isomers at the same time. Glycosaminoglycans were extracted by digestion with Pronase E, followed by digestion of GAGs with hyaluronidase SD and chondroitinase ACII. Unsaturated disaccharide isomers produced from hyaluronic acid and chondroitin sulfate were analyzed by high-performance liquid chromatography (HPLC). The hyaluronic acid disaccharide delta Di-HA was found in all samples of GCF, PISF and whole saliva. The concentration of delta Di-HA in both GCF and whole saliva of the periodontitis group was greater than that in the controls. There was no difference in the concentration of delta Di-HA between the PISF and GCF of the controls. The ratios of hyaluronic acid to chondroitin sulfate in the GCF and in the whole saliva of the periodontitis group were significantly lower than that of the controls. There was no difference between the ratios in PISF and those in GCF of the controls. These results indicate that checking hyaluronic acid in GCF and whole saliva using HPLC is a useful means of assessing the condition of periodontal tissues, and that assaying hyaluronic acid in PISF may also be effective for monitoring the condition of tissues around dental implants.
Asunto(s)
Líquido del Surco Gingival/química , Ácido Hialurónico/análisis , Periodontitis/diagnóstico , Adulto , Biomarcadores , Sulfatos de Condroitina/análisis , Cromatografía Líquida de Alta Presión , Implantes Dentales , Estudios de Evaluación como Asunto , Humanos , Persona de Mediana Edad , Saliva/químicaRESUMEN
Glycosaminoglycan (GAG) was extracted from monkey periodontium, consisting of gingiva, periodontal ligament, alveolar bone and cementum, and from dental pulp and dentin by digestion with Pronase E. Unsaturated disaccharide isomers formed by chondroitinase AC digestion from chondroitin sulfate were labeled with dansylhydrazine and analyzed by high-performance liquid chromatography. These tissues showed different molar ratios of the unsaturated chondroitin sulfate disaccharides. The ratio of delta Di-4S to delta Di-6S was lowest in the dental pulp, followed by the gingiva, periodontal ligament, dentin, alveolar bone, and cementum, in that order. It was greater in the calcified than in the uncalcified tissues.